Critical link between TRAIL and CCL20 for the activation of TH2 cells and the expression of allergic airway disease

Markus Weckmann, Adam Collison, Jodie L. Simpson, Matthias V. Kopp, Peter A.B. Wark, Mark J. Smyth, Hideo Yagita, Klaus I. Matthaei, Nicole Hansbro, Bruce Whitehead, Peter G. Gibson, Paul S. Foster, Joerg Mattes*

*Korrespondierende/r Autor/-in für diese Arbeit
94 Zitate (Scopus)

Abstract

The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (TH2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10-/-) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits T H2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10-/- mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.

OriginalspracheEnglisch
ZeitschriftNature Medicine
Jahrgang13
Ausgabenummer11
Seiten (von - bis)1308-1315
Seitenumfang8
ISSN1078-8956
DOIs
PublikationsstatusVeröffentlicht - 11.2007

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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